Neovascularized devices and biopolymer scaffolds are getting a great attention for their potential to improve islet transplantations. Among many biomaterials sources, human amniotic membrane (HAM) is considered as a natural source to produce ECM-based hydrogels with immunomodulatory, anti-inflammatory and antifibrotic properties. Here we develop an ECM-based hydrogel (Amniogel) derived from HAM and evaluate its potential to support islet function in vitro and in vivo.